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The Modulation of Pain by Circadian and Sleep-Dependent Processes: A Review of the Experimental Evidence

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Women in Mathematical Biology

Part of the book series: Association for Women in Mathematics Series ((AWMS,volume 8))

Abstract

This proceedings paper is the first in a series of three papers developing mathematical models for the complex relationship between pain and the sleep–wake cycle. Here, we briefly review what is known about the relationship between pain and the sleep–wake cycle in humans and laboratory rodents in an effort to identify constraints for the models. While it is well accepted that sleep behavior is regulated by a daily (circadian) timekeeping system and homeostatic sleep drive, the joint modulation of these two primary biological processes on pain sensitivity has not been considered. Under experimental conditions, pain sensitivity varies across the 24 h day, with highest sensitivity occurring during the evening in humans. Pain sensitivity is also modulated by sleep behavior, with pain sensitivity increasing in response to the build-up of homeostatic sleep pressure following sleep deprivation or sleep disruption. To explore the interaction between these two biological processes using modeling, we first compare the magnitude of their effects across a variety of experimental pain studies in humans. To do this comparison, we normalize the results from experimental pain studies relative to the range of physiologically meaningful stimulation levels. Following this normalization, we find that the estimated impact of the daily rhythm and of sleep deprivation on experimental pain measurements is surprisingly consistent across different pain modalities. We also review evidence documenting the impact of circadian rhythms and sleep deprivation on the neural circuitry in the spinal cord underlying pain sensation. The characterization of sleep-dependent and circadian influences on pain sensitivity in this review paper is used to develop and constrain the mathematical models introduced in the two companion articles.

The original version of this chapter was revised. An erratum to this chapter can be found at https://doi.org/10.1007/978-3-319-60304-9_13

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Acknowledgements

This work was conducted as a part of A Research Collaboration Workshop for Women in Mathematical Biology at the National Institute for Mathematical and Biological Synthesis, sponsored by the National Science Foundation through NSF Award DBI-1300426, with additional support from The University of Tennessee, Knoxville. This work was additionally partially supported by the following sources: NSF Award DMS-1412119 (VB), NSF RTG grant DMS-1344962 (JC), and the Pritzker Neuropsychiatric Disorders Research Consortium (MH). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

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Authors and Affiliations

  1. Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA

    Megan Hastings Hagenauer

  2. Department of Mathematical Sciences, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Jennifer A. Crodelle

  3. Department of Applied Mathematics and Computer Science, Technical University of Denmark, 2800, Kongens Lyngby, Denmark

    Sofia H. Piltz

  4. Biology Department, Washington and Lee University, Lexington, VA, 24450, USA

    Natalia Toporikova

  5. Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, 35487, USA

    Paige Ferguson

  6. Department of Mathematics, University of Michigan, Ann Arbor, MI, 48109, USA

    Victoria Booth

  7. Department of Anesthesiology, University of Michigan, Ann Arbor, MI, 48109, USA

    Victoria Booth

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  1. Megan Hastings Hagenauer
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  2. Jennifer A. Crodelle
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Correspondence to Victoria Booth .

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  1. Department of Mathematics, Duke University, Durham, North Carolina, USA

    Anita T. Layton

  2. Departments of Mathematics and Biology, University of North Carolina, Chapel Hill, North Carolina, USA

    Laura A. Miller

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Hagenauer, M.H., Crodelle, J.A., Piltz, S.H., Toporikova, N., Ferguson, P., Booth, V. (2017). The Modulation of Pain by Circadian and Sleep-Dependent Processes: A Review of the Experimental Evidence. In: Layton, A., Miller, L. (eds) Women in Mathematical Biology. Association for Women in Mathematics Series, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-60304-9_1

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